We wish to continue our long range study of the yeast hexokinase isoenzymes with the aim of understanding the chemical basis for: (a) their catalytic activity, (b) their subunit interactions, and (c) the metabolic regulation of their activities. More specifically, this will involve: (a-1) chemical characterization of the newly discovered phospho-enzyme derivative which results from inactivation of the enzyme with ATP plus D-xylose; (a-2) correlation of conformational changes with substrate binding; (b-1) further studies on the effects of alteration in N-terminal structure on the strength of subunit interactions; (b-2) comparison of the catalytic activities of the monomeric and dimeric forms of the enzyme; (c-1) study of the kinetics of the regulation of isoenzyme P-II by inhibitory and activating metabolites; (c-2) computer simulation of these kinetics with enzyme models involving no subunit interactions; (c-3) measurement of binding of activators and inhibitors to the enzyme-substrate complex.